The 2015 Dietary Guidelines have been released, and some supposedly significant changes, advised. Cholesterol intake is no longer limited. Saturated fat is to represent < 10% of daily caloric intake. Sustainability considerations are now to be considered. Simple sugars are anathema and caffeine is okay. Vegetables and fruits remain highly emphasized. Has much changed? Not really. Most of us in Cardiology and Lipidology dropped the cholesterol ban a decade ago. We typically emphasize fresh fruits and vegetables, low fat meat that is organic and devoid of antibiotics, and a limitation of simple sugar. Most of us don’t consider sustainability issues when advising our individual patients. Many of us believe that world issues – including economics – should stay out of the exam room and remain in the courtroom. (I am a member of that camp). But what is the layperson to do with these Guidelines? Does he or she have to make dramatic changes in his or her diet? The answer of course depends upon the individual patient’s status. Is weight loss necessary; does the patient have cardiovascular disease or very high LDL cholesterol, for instance? Let’s first look at the history of man, briefly examine the state of dietary literature, and then make some generalizations.

Anthropology unequivocally demonstrates that human beings are omnivores. In fact, all of our primate relatives also rely upon meat in the wild. They even need it in captivity. When the Washington DC Zoo attempted to breed the Amazon Golden Marmoset monkey, they failed miserably. It was not until meat was added to their diet that the monkeys begin to thrive and reproduce. Since the beginning of our tour on earth we have also eaten meat. In fact, for the first 4 million years of our existence, meat was our main source of nourishment. About 10,000 years ago we introduced farming and animal husbandry. Most farming was done to feed our animals as they represented our most desirable food source. Recently we have fallen prey to our own impact on nourishment – we have started processing, and ruining, our food. Sugar has been added; nutrients have been stripped from grains; grains are squeezed (instead of eaten whole) to produce oils; and animals have been raised in pens, limiting their ability to develop lean muscle mass, and also often requiring the introduction of antibiotics. We have created a food supply that is most likely killing us.

In response to our understanding of the role cholesterol plays in heart disease – and it does play a significant one – we have introduced guidelines to try to reduce cholesterol. Saturated fat eaten to excess does raise LDL (not a good thing), but cholesterol consumption has little impact on our LDL levels. Therefore the current Guidelines did what was appropriate and removed restrictions on cholesterol consumption while maintaining limitations on saturated fat. They also appropriately implore us to eschew sugar. No one will argue against the latter recommendation (except perhaps the sugar industry). But are there studies to support such advice? Unfortunately, beyond PrediMed (which demonstrated the cardiovascular advantage of a Mediterranean diet) no high level studies have been performed. Many observational studies exist, but doing a solid dietary trial is actually immensely difficult. Thus we are left to rely upon our understanding of basic science, animal experiments, pathophysiology, and anthropology. The conclusion for most of us I believe follows Aristotle’s ancient tenet of moderation. We should consume natural foods whenever possible, avoid processed foods, eat copious quantities of vegetables, consume ample fruit, and don’t worry so much about consuming lean meat, fatty fish, and some chicken as well. We should do this in the context of seeing our physicians, discussing our own personal issues, and modifying our diets to adjust to individual needs when indicated. Eating has become a complex endeavor, yet it ought to be much more straightforward. What we need though is access to the aforementioned natural food, the type of food that has been unscathed by human hands. And therein, unfortunately, lies the rub.

Any doctor worth his salt recognizes that patients don’t always respond the way we anticipate they will. For example, utilizing the best of our scientific methodologies we know LDL is causally related to vascular disease. High LDL causes disease while low LDL mitigates it. Yet, we occasionally see patients with extraordinarily high LDL and no disease, as well as those with very low LDL and severe disease. In some circumstances, patients with a vascular disease promoting mutation – as in Familial Hypercholesterolemia – will have severe and premature heart disease while their relatives with the same mutation somehow remain unscathed. How can this be? What we’ve all come to believe is that there must be protective genes that somehow offset the detrimental aspects of other genes. Let’s dub these desired genes “Guardian Genes”.

In the case of vascular disease promoting disorders, Guardian genes cause the exception, not the rule. They Teflon coat individuals who under normal circumstances should develop heart attacks and strokes. This wonderful rarity can unfortunately lead to a misunderstanding of disease processes as well as their cures. When someone speaks of grandma whose LDL was 300 and yet lived to the ripe old age of 100, sans MI or stroke, the take-home message often is, “Those doctors don’t know what they’re talking about. LDL is not the cause of heart disease. My LDL is only 200 and as grandma lived to 100 and with worse numbers, why should I take that statin medicine. Just look at the Internet and you can see how terrible those medicines are.” Unfortunately the Guardian genes are currently merely speculative. As such we cannot identify them. And, we know that intra-family variability in development of vascular disease supports the notion that theses guardian genes are inherited entirely separately from the disease promoting genes. What that means is just because grandma won the lottery, don’t bet your life (literally) that you did as well. In my own practice I’ve seen 70-year-old parents mourn the deaths of their 40-year-old sons and daughters who died of MIs. Though they shared the same bad genes, the parents did not suffer the unfortunate (and more predictable fate) of their children.

The bottom line here is that we doctors must base our treatment recommendations on the odds. We weigh and measure the pros and cons of therapeutic options (like the statins) against the likelihood that an individual patient will develop a serious event such as a heart attack, stroke, or even death. We use our best judgment based upon many facets of knowledge and understanding. We then make our recommendations hoping to stave off future adverse cardiovascular events. We never risk a patient’s life hoping he or she has inherited a guardian gene. Until we identify the elusive lifesaver guardian genes they will remain relegated to being the modern day Holy Grail of genetics. We all pray we will find them, but until that day we must continue to practice within the limits of our understanding. And while we do, we hope our patients understand that our suggestions and recommendations are born of both a deep understanding of the science of medicine and the burning desire to help our patients live the longest and best lives possible.

Tomorrow morning a large crowd will gather here at the AHA meetings in frigid Chicago to learn the findings of the long-awaited IMPROVE-IT trial. The trial will demonstrate whether or not Ezetamibe (Zetia) added to a Simvastatin (Zocor) successfully decreased cardiovascular events in high-risk patients.

Many lipid specialists and cardiologists, myself included, have used Ezetamibe in combination with statins since the drug’s release. We believe wholeheartedly in the “lower LDL is better” hypothesis. Our clinical results, though anecdotal, have been uniformly exceptional. We fully anticipate that – barring confounding circumstances – the trial will be a winner.

Making this prospect even more impactful is the current NEJM publication by Dr. S. Kathiresan, (a brilliant Harvard Cardiologist/Geneticist) describing a novel genetic mutation that decreases LDL cholesterol, and concomitantly reduces ASCVD events. Where is this mutation you might ask: In the same receptor that is blocked by the drug Ezetamibe. Essentially individuals bearing such a mutation are born with the equivalent of continual Zetia use. This experiment of nature surely supports the speculation that Ezetimibe effectively lowers heart disease, even on top of statin therapy.

For now, we can only speculate about IMPROVE-IT’s findings. Tomorrow will bring some hard facts along with an assessment of how the findings will impact not only doctors’ use of Ezetamibe, but equally importantly, how health insurance companies will view the matter as well. Until tomorrow my admittedly unbiased fingers will be tightly crossed.

On October 13th the world’s “who’s who” in FH research and patient care convened in an oddly elongated New York City hotel meeting room. For two days the group shared novel information, spontaneous ideas, well-conceived proposals for future research, and even heart wrenching stories from a handful of brave and resilient FH patients. Windowless room notwithstanding, leaders from the Netherlands, South Africa, Australia, Chile, Russia, France, Sweden, Oman and the US uniformly basked in the bliss of a mutual goal, raising awareness and improving treatment for this far too common and oft-unrecognized disease.

Some of the highlights included a one-year review of the FH Foundation’s CASCADE FH Registry. We were all pleased and proud to learn that the Registry had surpassed its forecast goal by over 30% (Actually by over 400% of a more modest prediction). We travelled the world identifying FH “Gaps Across the Globe.” During this session leaders from diverse nations compared and contrasted barriers to care, offering useful methods to hurdle such obstacles. We heard from a continuum of clinicians – internists, lipid specialists, endocrinologists, cardiologists, and gastroenterologists – as well as PhDs occupying a wide range of disciplines. To say the conference was comprehensive fails to express its exceptionality. It was a time apart from other times, a transcendent growth opportunity for all those fortunate enough to be in attendance. It will surely serve as a solid springboard for meaningful clinical collaborations throughout the next year.

In sum, the 2014 FH Global Summit was so spectacular it will be hard to surpass in 2015. However, considering the passion and energy shared by members of the FH Foundation and colleagues across the globe, I feel safe in predicting that 2015 will exceed even the extraordinariness of this year’s event.

I spent Thursday and Friday in California. No, I wasn’t strolling on the beach or sipping local wines. Instead, I was engaged in strategic conversations during our FH Foundation Board of Directors Annual meeting. FH (Familial Hypercholesterolemia), as you know from prior posts, (if you don’t, please visit www.thefhfoundation.org or see my older blogs and FH/cholesterol articles at www.preventivecardiologyinc.com) is a common yet terribly underdiagnosed genetic disorder that elevates LDL cholesterol which in turn causes early and life-threatening heart disease. Affected patients cover a wide spectrum, having disease from before age ten to as late as 70 or 80 years old. We spent some time examining last year’s accomplishments, but more importantly we determined how to continue the process of converting dreams into reality. I’ve chosen to share this story with you for two reasons: First, FH must be conquered. Second and no less important, the Foundation epitomizes the power of a small group driven by unfettered passion, enthusiasm, and commitment.

Katherine Wilemon, the group’s founder, CEO, and tireless leader, suffered her heart attack shortly after the birth of her daughter. Though she had lifelong high cholesterol, and had experienced symptoms before the event, her genetic disease was initially unrecognized. And, in medicine, to be able to provide appropriate care we usually must know what it is we’re treating. Fortunately for Katherine – and her family – she survived. Subsequently, wishing to turn a terrible event into a hopeful future, Katherine started the FH Foundation. That was just three years back. Since then, Katherine has not only surrounded herself with a growing group of highly effective and devoted patients, doctors, and businesspeople, she has travelled the world building awareness and interacting with every true FH expert. The FH Foundation has established a National FH Awareness Day. It has created the first and only Registry for FH patients in the US (Cascade FH). The FH Foundation spearheaded the establishment of ICD 10 codes for this disease, and it has initiated protocols to identify every single FH patient in our nation.

Our second Global FH Summit will take place this October in New York City. An array of nations will be represented. The list goes on and on. I recount this litany of achievements not to boast, but to demonstrate how the visions of an individual can burgeon, ultimately impacting the reality of so many. Coming away from two days of inspiring meetings I am certain the Foundation will continue to succeed. In short order FH will entirely emerge from the shadows. FH will become a disease on the tip of every doctor’s tongue, and consequently afflicted patients of all ages will no longer suffer and even die unnecessarily. Millions of people’s lives will be changed for the better. At the risk of being mawkish, I must state that my experience with the FH Foundation illuminated the fact that if more of us would only act with similar commitment and intention, we might just find ourselves in a peaceful and unified world. It’s a tall order I know, but the FH Foundation has given me a glimpse of the possibilities that can be born of the seemingly impossible.

Currently a debate rages in the world of Familial Hypercholesterolemia (FH). Old school thinking is that this lipid disorder – typically caused by a mutation in one of three genes – is exceedingly rare. The initial teaching stated that the homozygous form (two mutations – one from mother and one from father, HoFH) occurs at a rate of one in a million, while the heterozygous form (one mutation from just one parent, HeFH) occurs at a rate of one in 500. Recent explosions in not only genetics, but also the acquisition of large volumes of patient data have put this prior supposition in question. Now, a recent study published in the European Heart Journal by Sjouke et al truly proves that we have grossly underestimated the prevalence of FH. Examining over 100,000 patients who were referred for genetic analysis, the authors found 74 patients with clinically significant mutations consistent with the homozygous form of FH (HoFH). Being abundantly cautious in their interpretation of data, the authors pared the number down to just 45, from which they conducted a mathematical calculation of the prevalence of FH. (Their minimalist rationale is beyond the scope of this blog, but suffice it to say that had they included all patients, the disease prevalence would be far greater). Their restrained assessment revealed the prevalence of HoFH in an unselected population to be 1 in about 300,000 while the prevalence of HeFH, 1 in 244.

Perhaps more striking and even earthshattering is what the authors discovered about the wide range of HoFH LDL-C levels. Older belief systems had maintained that the LDL-C in untreated HoFH should always exceed about 450 mg/dL. In their comprehensive and novel analysis however, the authors discovered untreated HoFH patients with LDL-C levels as low as 170 mg/dL. 170 mg/dL overlaps not only the HeFH population, but the non-FH population as well. The bottom line here once again is that as in diagnosing all other diseases, clinicians must maintain open minds when diagnosing FH. When considering FH, we must always look for a family history of premature vascular disease, very high LDL-C levels, signs of the disorder on physical examination, and the presence of aggressive coronary artery or cerebro-vascular disease in the patient we are evaluating. Most important is for all clinicians to keep FH on the tips of our tongues. Without considering the diagnosis, we will never make it. And without making the diagnosis, we will never treat it. Early treatment can be life saving so early diagnosis is of course paramount. In no other lipid disorder is the concept that “Time is Plaque” more apparent. FH patients bathe in their own LDL-C in utero and beyond. The longer they remain untreated the worse they do. So let’s think of FH and treat it when we see it. By doing so we can hope to prolong the lives of more than a million people right here in the USA.

Recently, after participating in a meeting attended by a few high-powered CVD researchers I returned home plagued by a most simplistic question: What is the purpose of LDL cholesterol? Please refrain from bursting into uncontrollable spasms of laughter; I am well aware that as a clinical lipidologist I never imagined such a question would have the capacity to keep me up at night. And yet it did. And so I called my faithful counsel, upon whom I can always rely to extricate me from any lipid conundrum. Tom Dayspring responded to my query unflustered, promptly sending me articles to help me find my way. I read them and this is what I realized. LDL cholesterol is essentially garbage. The story goes something like this.

Our livers manufacture triglyceride – (TG) and cholesterol – containing lipoprotein particles called VLDLs. This is old news. VLDL contains about 80% TG and 20% cholesterol. Its purpose is to nourish our organs. As these particles pass through the tiny capillaries of our various organs, enzymes called Lipoprotein Lipase (LPL) snip the fatty acids from their TG backbone, Glycerol. This too is old news. These released fatty acids are either used for energy or stored by our organs for future needs. The shrunken down VLDL particles, devoid of most of their TG energy content, are now re-dubbed. They have become LDL particles. They are cholesterol-rich. Their content represents what most people speak about after visiting their doctors – LDL-C or LDL cholesterol. Here’s where it gets intriguing. Although any lipid specialist can tell you that every single cell in our body has the capacity to make cholesterol, most believe that the cholesterol contained in LDL particles has some greater purpose. Our cells however do not need the cholesterol contained in LDL particles; nonetheless, most of us believe they use it. This belief is untrue. LDL-C is actually not utilized to any significant degree by any organ systems in human beings. Other animals may use some of it here and there, but not us. We just don’t need it. In fact, the goal of LDL particles is to get to the liver ASAP for disposal. Otherwise, these particles tend to land in places where we do not want or need them, our blood vessel walls to be more specific. You know how that story goes – plaque forms; plaque ruptures; heart attacks or strokes ensue…

So when people tell you not to worry about your high LDL-C levels, please reconsider abandoning your doctor’s LDL-C-lowering advice. And definitely don’t worry that low LDL-C levels will deprive your cells of their much-needed cholesterol. It won’t. Your cells are quite capable of making their own supply of cholesterol. On a somewhat esoteric note, it is true that the surface of LDL particles transports some vital nutrients around the body (vitamin E for one). This fact however does not imply that more LDL is better than less. We need just a tiny bit for non-cholesterol purposes. Excess does us no good, and in truth it does us a good deal of harm.

Familial Hypercholesterolemia (FH) is a genetic disorder of LDL cholesterol handling which can lead to heart attack and stroke at very young ages. You may be shocked to learn that afflicted children as young as four years old have required bypass surgery or even perished from heart attacks. More surprising still is the fact that we now recognize that FH is far more common than previously believed. Some studies indicate that one in 200 people has a “milder” form of the disease, while one in 160,000 suffers from its most severe variant. It’s all FH though, and even in mild cases the risk of heart attack can be 20 times that of a “normal” individual. Heart attacks in such cases occur much earlier in life than would ordinarily be anticipated. Here’s an example to which everyone can relate. 20% of patients who have heart attacks under the age of 45 have FH. Consider all the young people you know who’ve had heart attacks. One fifth of them probably have this genetic disorder. That is a huge number. The most recent estimate puts the number of FH patients in the US at 1 to 2 million. So that is certainly not rare! The number of extraordinarily severe cases is probably between 2 and 3 thousand, qualifying for the definition of a rare disease – being fewer than 200,000 in the US. Distressingly, only about 10% of FH patients have been identified as having the disease. That leaves 90% unrecognized, undertreated, and at great risk. We must change this pattern.

It is imperative on this Rare Disease Day that we all do our part to spread the word about FH. If you or someone you love has an LDL-C greater than 190 mg/dL you very likely bear this genetic malady. That means every one of your first-degree relatives – parents, siblings, and yes, even your children – has at least a 50% chance of also having the disease. Early treatment is key to improving outcomes. That’s why we recommend all children with a family history of premature heart disease or very high LDL cholesterol have their initial cholesterol level checked at the age of 2. By identifying family members with FH we can then treat them accordingly. Early recognition saves lives, sparing families the agony of losing a young, vibrant relative in the prime of her life. The good news is that there is much we can offer patients with FH. Novel medications and procedures such as LDL apheresis can dramatically lower LDL levels.

To learn more about such treatment strategies, please visit the FH Foundation at thefhfoundation.org. If you believe you might have FH, please join our National Registry, the CASCADE FH Registry and become one of the many people who will help us curtail the terrible toll FH often takes. We look forward to hearing from you!

Okay. You read the title and immediately imagined a bunch of doctors and scientists lounging on the spectacular Mexican beaches while you – if you live pretty much anywhere in the US – dig yourself out from yet another snowfall. It is true that the beach is pristine. And yes, the weather is unbeatable. But, truth be told, every speaker and attendee spent days and evenings continually holed up in a windowless conference room discussing issues ranging from exercise and diet, to Familial Hypercholesterolemia (FH), to even the impact of COPD on CVD. The meeting was excellent. Great discussions, proposals for future collaborations, some colleagues reuniting while others being introduced to a new group of associates. The ACC/AHA Cholesterol and Risk Assessment Guidelines as well as the new BP Guidelines were hotly debated.

In all, it was a wonderful weekend that enabled us to exchange ideas, consider alternate approaches to our patients, and simply grow as doctors, nutritionists, and scientists. So while American Medicine continues to be a target of mostly criticism, rest assured there are many who continue to do their part to ensure the viability and continuation of truly top-notch healthcare and research.